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2.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462009

RESUMO

Subretinal fluid accumulation in a patient with systemic lupus erythematosus (SLE) may represent a diagnostic challenge. We present a case of a 43-year-old man with baseline diagnosis of SLE and hydroxychloroquine-associated maculopathy who reported progressive vision loss on the right eye, associated with corticosteroids use for an arthritic crisis. Ophthalmological examination did not reveal any acute finding. On optical coherence tomography, subretinal fluid in the perifoveal area was visible on the right eye, with corresponding enlargement of the visual field defect. An increased choroidal thickness was also visible. Fluorescein angiography revealed, on the right eye, two pinpoint areas of leakage and indocyanine green angiography signs of choroidal vascular hyperpermeability. Considering a diagnosis of a non-central central serous chorioretinopathy, corticosteroids use was interrupted, with resolution of the subretinal fluid. This case illustrates the relevance of a multimodal imaging approach to guide the diagnosis of patient with an SLE with subretinal fluid.


Assuntos
Corticosteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Hidroxicloroquina/efeitos adversos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Retinianas/induzido quimicamente , Corticosteroides/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Masculino , Doenças Retinianas/diagnóstico
3.
J Vis Exp ; (163)2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-33016936

RESUMO

One of the commonly used models for ischemic retinopathies is the oxygen-induced retinopathy (OIR) model. Here we describe detailed protocols for the OIR model induction and its readouts in both mice and rats. Retinal neovascularization is induced in OIR by exposing rodent pups either to hyperoxia (mice) or alternating levels of hyperoxia and hypoxia (rats). The primary readouts of these models are the size of neovascular (NV) and avascular (AVA) areas in the retina. This preclinical in vivo model can be used to evaluate the efficacy of potential anti-angiogenic drugs or to address the role of specific genes in the retinal angiogenesis by using genetically manipulated animals. The model has some strain and vendor specific variation in the OIR induction which should be taken into consideration when designing the experiments.


Assuntos
Modelos Animais de Doenças , Isquemia/induzido quimicamente , Oxigênio/farmacologia , Doenças Retinianas/induzido quimicamente , Animais , Isquemia/complicações , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/fisiopatologia , Doenças Retinianas/complicações , Neovascularização Retiniana/complicações
4.
Eur J Pharmacol ; 886: 173454, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32763298

RESUMO

Antimalaria drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been administered to several inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus, and infectious diseases such as acquired immune deficiency syndrome and influenza. Recently, several patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were given HCQ, and showed a discrepant response. HCQ inhibits SARS-CoV-2 cell entry, and inflammatory cascade by interfering with lysosomal and endosomal activities, and autophagy, impeding virus-membrane fusion, and inhibiting cytokine production resulted from inflammatory pathways activation. Despite ongoing administration of HCQ in a wide spectrum of disorders, there are some reports about several side effects, especially retinopathy in some patients treated with HCQ. Cytochrome P450 (CYP450) and its isoforms are the main metabolizers of HCQ and CQ. Pharmacokinetic properties of CYP enzymes are influenced by CYP polymorphism, non-coding RNAs, and epigenetic mechanisms such as DNA methylation, and histone acetylation. Accumulating evidence about side effects of HCQ in some patients raise the possibility that different response of patients to HCQ might be due to difference in their genome. Therefore, CYP450 genotyping especially for CYP2D6 might be helpful to refine HCQ dosage. Also, regular control of retina should be considered for patients under HCQ treatment. The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy.


Assuntos
Betacoronavirus/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Epigênese Genética/efeitos dos fármacos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Doenças Retinianas/induzido quimicamente , Humanos , Isoenzimas/genética , Doenças Retinianas/genética
5.
J Fr Ophtalmol ; 43(8): 727-730, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620415

RESUMO

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.


Assuntos
Monitorização Fisiológica , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Tamoxifeno/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Macula Lutea/efeitos dos fármacos , Macula Lutea/patologia , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Monitorização Fisiológica/métodos , Doenças Retinianas/patologia , Tamoxifeno/administração & dosagem , Tomografia de Coerência Óptica
6.
J Cardiovasc Pharmacol Ther ; 25(6): 497-502, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32700555

RESUMO

In recent months, the new coronavirus SARS-CoV-2 has emerged as a worldwide threat with about 4.2 million confirmed cases and almost 300 000 deaths. Its major clinical presentation is characterized by respiratory symptoms ranging from mild cough to serve pneumonia with fever and potentially even death. Until today, there is no known medication to improve clinical symptoms or even prevent or fight the infection. The search for a useful vaccination is ongoing and it will probably not be available before the end of 2020. In this review, we highlight hydroxychloroquine (HCQ) as a potential agent to prevent coronavirus disease 2019 (COVID-19) and reduce as well as shorten clinical symptoms. Moreover, it might serve as a potential post-exposition prophylaxis. Although it has been used in the treatment of rheumatoid arthritis, discoid or systemic lupus erythematosus, and malaria prophylaxis and therapy for decades, knowledge on HCQ as a potential treatment for COVID-19 is limited and multiple clinical trials have just emerged. Especially, rare HCQ side effects which were of minor importance for use in selected indications might gain major relevance with population-wide application. These rare side effects include retinopathy and-even more important-QT prolongation leading to sudden cardiac death by malignant arrhythmias.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Pandemias , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Retinianas/induzido quimicamente
8.
Adv Rheumatol ; 60(1): 32, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517786

RESUMO

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Infecções por Coronavirus/tratamento farmacológico , Erupção por Droga/etiologia , Interações Medicamentosas , Feminino , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Humanos , Lipídeos/sangue , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pandemias , Agregação Plaquetária/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Gravidez , Insuficiência Renal/prevenção & controle , Doenças Retinianas/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia
9.
In Vivo ; 34(3 Suppl): 1619-1628, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503820

RESUMO

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.


Assuntos
Infecções por Coronavirus/complicações , Oftalmopatias/etiologia , Pneumonia Viral/complicações , Doenças do Nervo Abducente/etiologia , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Biomarcadores , China , Doenças da Túnica Conjuntiva/sangue , Doenças da Túnica Conjuntiva/etiologia , Lentes de Contato/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Contaminação de Equipamentos , Oftalmopatias/prevenção & controle , Humanos , Hiperemia/sangue , Hiperemia/etiologia , Imunização Passiva/efeitos adversos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Ceratoconjuntivite/etiologia , Doenças do Aparelho Lacrimal/sangue , Doenças do Aparelho Lacrimal/etiologia , Contagem de Leucócitos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Doenças Retinianas/induzido quimicamente , Estudos Retrospectivos
13.
Invest Ophthalmol Vis Sci ; 61(5): 32, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32428233

RESUMO

Purpose: Because air pollution has been linked to glaucoma and AMD, we characterized the relationship between pollution and retinal structure. Methods: We examined data from 51,710 UK Biobank participants aged 40 to 69 years old. Ambient air pollution measures included particulates and nitrogen oxides. SD-OCT imaging measured seven retinal layers: retinal nerve fiber layer, ganglion cell-inner plexiform layer, inner nuclear layer, outer plexiform layer + outer nuclear layer, photoreceptor inner segments, photoreceptor outer segments, and RPE. Multivariable regression was used to evaluate associations between pollutants (per interquartile range increase) and retinal thickness, adjusting for age, sex, race, Townsend deprivation index, body mass index, smoking status, and refractive error. Results: Participants exposed to greater particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) and higher nitrogen oxides were more likely to have thicker retinal nerve fiber layer (ß = 0.28 µm; 95% CI, 0.22-0.34; P = 3.3 × 10-20 and ß = 0.09 µm; 95% CI, 0.04-0.14; P = 2.4 × 10-4, respectively), and thinner ganglion cell-inner plexiform layer, inner nuclear layer, and outer plexiform layer + outer nuclear layer thicknesses (P < 0.001). Participants resident in areas of higher levels of PM2.5 absorbance were more likely to have thinner retinal nerve fiber layer, inner nuclear layer, and outer plexiform layer + outer nuclear layers (ß = -0.16 [95% CI, -0.22 to -0.10; P = 5.7 × 10-8]; ß = -0.09 [95% CI, -0.12 to -0.06; P = 2.2 × 10-12]; and ß = -0.12 [95% CI, -0.19 to -0.05; P = 8.3 × 10-4], respectively). Conclusions: Greater exposure to PM2.5, PM2.5 absorbance, and nitrogen oxides were all associated with apparently adverse retinal structural features.


Assuntos
Poluição do Ar/efeitos adversos , Fibras Nervosas/efeitos dos fármacos , Óxidos de Nitrogênio/efeitos adversos , Material Particulado/efeitos adversos , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Células Ganglionares da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Adulto , Idoso , Bancos de Espécimes Biológicos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Células Fotorreceptoras de Vertebrados/patologia , Doenças Retinianas/induzido quimicamente , Células Ganglionares da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/patologia , Inquéritos e Questionários , Tomografia de Coerência Óptica , Reino Unido
14.
Am J Ophthalmol ; 218: 28-39, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32445701

RESUMO

PURPOSE: To compare outcomes of patient who underwent surgery using perfluorooctane (PFO; C8F18; Ala Octa) with those who underwent surgery with perfluorodecalin (F-Decalin). DESIGN: Retrospective, consecutive, comparative, interventional case series. METHODS: A total of 48 eyes that underwent vitrectomy with PFO were compared to 29 eyes that underwent vitrectomy with perfluorodecalin. Two experienced surgeons performed vitrectomies at the Geneva University Eye Clinic. Visual acuity before, at 8 and 24 weeks after surgery, was documented, and spectral domain optical coherence tomography (SD-OCT) images were analyzed for abnormalities. RESULTS: Two patients experienced severe retinal toxicity, including 1 with severe vision loss. However, no statistical differences in VA were observed between the PFO and perfluorodecalin patients. Analysis of SD-OCT images showed differences in occurrence of several abnormalities, for example, inner segment-outer segment alterations were found in 60.4% of eyes treated with PFO and in 10.3% of perfluorodecalin-treated eyes; retinal atrophic areas were found in 41.7% of PFO and in none of the perfluorodecalin eyes; inner limiting membrane contraction was found in 58.4% of PFO and in none of perfluorodecalin eyes; inner retina cystic alterations were found in 58.3% of PFO eyes and 17.2% of perfluorodecalin eyes; outer retina cystic alterations were found in 39.6% of PFO eyes and 13.8% of perfluorodecalin eyes; retinal holes were found in 14.6% of PFO eyes and in none of the perfluorodecalin eyes; and outer retinal inclusions were found in 20.8% of PFO eyes and in 3.45% of perfluorodecalin eyes. CONCLUSIONS: Perfluorooctane caused significantly more toxic damage than perfluorodecalin. Special consideration should be given to develop a central European Union (EU) control agency for medical devices and to reevaluate safety procedures currently accepted by the EU and International Organization for Standardization for intraocular surgery.


Assuntos
Migração do Implante de Lente Intraocular/cirurgia , Corpos Estranhos no Olho/cirurgia , Fluorcarbonetos/toxicidade , Retina/efeitos dos fármacos , Descolamento Retiniano/cirurgia , Doenças Retinianas/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tamponamento Interno , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos , Suíça , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Vitrectomia
15.
Asia Pac J Ophthalmol (Phila) ; 9(2): 85-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32349115

RESUMO

The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.


Assuntos
Cloroquina/toxicidade , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/toxicidade , Pneumonia Viral/tratamento farmacológico , Retina/efeitos dos fármacos , Betacoronavirus , Cloroquina/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Pandemias , Retina/patologia , Doenças Retinianas/induzido quimicamente , Fatores de Risco
19.
Clin Nephrol ; 93(3): 149-151, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31983382

RESUMO

Hydroxychloroquine (HCQ) has become the rheumatologists's "Swiss army knife" when it comes to managing the rheumatologic manifestations of SLE and other auto-immune disorders. By contrast, nephrologists are much less comfortable in managing the multifaceted effect of HCQ. As a result, nephrologists are inclined to abdicate their responsibility for HCQ management, if this therapy was initiated by a rheumatologist. This report describes such a situation, which had devastating consequences for the patient. On this basis we suggest that this report is a story worth telling, and should encourage the nephrologist to be more involved in their patients' HCQ management.


Assuntos
Antirreumáticos/toxicidade , Hidroxicloroquina/toxicidade , Nefrologistas , Adulto , Feminino , Humanos , Rim/efeitos dos fármacos , Lúpus Eritematoso Sistêmico/complicações , Doenças Retinianas/induzido quimicamente
20.
Lupus ; 29(3): 283-289, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31992127

RESUMO

OBJECTIVE: To evaluate ocular involvement in a cohort of systemic lupus erythematosus (SLE) patients of a tertiary referral center and to compare the results with the existing literature. METHODS: Patients underwent a complete ophthalmological evaluation, including visual acuity, slit-lamp examination, fluorescein staining, Schirmer-I test, Goldmann applanation tonometry, fundoscopy, 10-2 automated threshold visual fields, fundus autofluorescence and spectral-domain optical coherence tomography to screen for hydroxychloroquine (HCQ) macular toxicity. RESULTS: A total of 161 patients (16 men and 145 women) were enrolled in this study. The mean age was 47.6 years and the mean disease duration was 11.5 years. Fifty patients (31.1%) had at least one ocular manifestation of SLE. The most frequent manifestation was dry eye syndrome (12.4%), immediately followed by cataracts (11.2%) and HCQ macular toxicity (11.2%). Among patients with HCQ maculopathy, two presented with an atypical spectral-domain optical coherence tomography pattern. Five patients (3.1%) presented with glaucoma, two patients (1.2%) presented with SLE retinopathy while only one presented with lupus choroidopathy (0.6%). CONCLUSIONS: Compared with previous studies, we conclude there has been a significant reduction in disease-related ocular complications, particularly those associated with poor systemic disease control. On the other hand, drug and age-related complications are assuming a prominent role in the ophthalmic care of these patients.


Assuntos
Oftalmopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Antirreumáticos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Oftalmopatias/diagnóstico , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Centros de Atenção Terciária , Tomografia de Coerência Óptica , Acuidade Visual
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